Neuromodulation of Mood Switch Circuitry in Bipolar Disorder

Summary

This study is exploring a new approach to treating depression in people with bipolar disorder (BD). Investigators are testing whether a non-invasive form of brain stimulation can help us understand depressed-to-euthymic mood shifts and their related brain circuits in BD.

Investigators in this study will use a technique called repetitive transcranial magnetic stimulation, or rTMS. It uses non-invasive magnetic pulses delivered to the scalp to stimulate specific areas of the brain. rTMS is already used to treat depression, and investigators are now studying whether it can be made even more effective for people with bipolar disorder by precisely targeting an individualized brain region for each participant. Participants in this study will receive two courses of rTMS, one active and one placebo (called "sham"), in a randomized order so investigators can directly compare the effects. Before treatment, investigators will use brain scans (MRI) to create a personalized map of each participant's brain activity. This lets investigators identify the exact stimulation target most likely to influence the brain circuits involved in BD mood shifts. Investigators will track mood symptoms closely throughout the study to measure what changes.

Investigators believe that depression in BD is partly driven by disrupted communication between two brain regions involved in processing what feels important or rewarding. Investigators want to find out whether rTMS can restore that communication and whether doing so leads to measurable improvements in depression.

Conditions

• Bipolar Disorder (BD)
• Bipolar 1 Depression
• rTMS
• fMRI

Interventions

DEVICE

MagVenture MagPro TMS system

TANS-guided SAL Acc iTBS approach: Targeted Functional Network Stimulation (TANS) combines precision functional mapping (PFM) with electric field (E-field) modeling to individualize circuit targeting. Active rTMS will be intermittent theta burst simulation (iTBS) delivered to the salience network (SAL) with an accelerated intervention protocol (up to 5 consecutive days of 10 hourly active rTMS sessions).

DEVICE

Sham Stimulation

An Active/Placebo (A/P) sham TMS coil will be used to deliver placebo stimulation. The A/P coil is a double-sided coil in which one side delivers effective magnetic stimulation, while the opposite side is configured to produce a sham condition without inducing cortical activation. Sham stimulation will also be delivered to the salience network (SAL) with an accelerated intervention protocol (up to 5 consecutive days of 10 hourly sham rTMS sessions).

Sponsors & Collaborators

• BD2 LLC

  collaborator UNKNOWN

• Weill Medical College of Cornell University

  lead OTHER

Principal Investigators

• Immanuel Elbau, MD, PhD · Weill Medical College of Cornell University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-07-31

Primary Completion

2031-09-30

Completion

2031-12-31

FDA Device

Yes

Countries

• United States

Study Locations